Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida, USA.
Department of Biological Sciences, Ohio University, Athens, Ohio, USA.
J Bacteriol. 2020 Dec 18;203(2). doi: 10.1128/JB.00293-20.
utilizes numerous metabolite transporters to obtain essential nutrients in the "feast or famine" environment of the human mouth. and most other streptococci are considered auxotrophic for several essential vitamins including riboflavin (vitamin B), which is used to generate key cofactors and to perform numerous cellular redox reactions. Despite the well-known contributions of this vitamin to central metabolism, little is known about how obtains and metabolizes B The uncharacterized protein SMU.1703c displays high sequence homology to the riboflavin transporter RibU. Deletion of hindered growth in complex and defined medium in the absence of saturating levels of exogenous riboflavin, whereas deletion of cotranscribed alone had no apparent effect on growth. Expression of in a riboflavin auxotroph functionally complemented growth in nonsaturating riboflavin conditions. was also able to grow on flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN) in an SMU.1703c-dependent manner. Deletion of and/or impacted acid stress tolerance, as all mutants showed improved growth at pH 5.5 compared to that of the wild type when medium was supplemented with saturating riboflavin. Cooccurrence of and , a hypothetical PAP2 family acid phosphatase gene, appears unique to the streptococci and may suggest a connection of SMU.1702c to the acquisition or metabolism of flavins within this genus. Identification of SMU.1703c as a RibU-like riboflavin transporter furthers our understanding of how acquires essential micronutrients within the oral cavity and how this pathogen successfully competes within nutrient-starved oral biofilms. Dental caries form when acid produced by oral bacteria erodes tooth enamel. This process is driven by the fermentative metabolism of cariogenic bacteria, most notably Nutrient acquisition is key in the competitive oral cavity, and many organisms have evolved various strategies to procure carbon sources or necessary biomolecules. B vitamins, such as riboflavin, which many oral streptococci must scavenge from the oral environment, are necessary for survival within the competitive oral cavity. However, the primary mechanism and proteins involved in this process remain uncharacterized. This study is important because it identifies a key step in riboflavin acquisition and cofactor generation, which may enable the development of novel anticaries treatment strategies via selective targeting of metabolite transporters.
利用众多代谢物转运蛋白在人类口腔的“饱食或饥饿”环境中获取必需营养物质。大多数其他链球菌被认为是几种必需维生素的营养缺陷型，包括核黄素（维生素 B），核黄素用于生成关键辅因子和进行许多细胞氧化还原反应。尽管这种维生素对中心代谢有众所周知的贡献，但对于如何获取和代谢 B 知之甚少。未被表征的蛋白质 SMU.1703c 与核黄素转运蛋白 RibU 具有高度序列同源性。在没有饱和水平外源核黄素的情况下，缺失 会阻碍在复杂和定义的培养基中的生长，而单独缺失共转录的 对生长没有明显影响。在核黄素营养缺陷型中表达 可在非饱和核黄素条件下功能性地补充生长。还能够以依赖 SMU.1703c 的方式在黄素腺嘌呤二核苷酸 (FAD) 或黄素单核苷酸 (FMN) 上生长。缺失 和/或 会影响 酸应激耐受性，因为所有突变体在 pH 5.5 时与野生型相比，在培养基中补充饱和核黄素时生长情况得到改善。 和假设的 PAP2 家族酸性磷酸酶基因 的共存似乎仅在链球菌中出现，这可能表明 SMU.1702c 与该属中黄素的获取或代谢有关。将 SMU.1703c 鉴定为类似于 RibU 的核黄素转运蛋白，进一步加深了我们对 如何在口腔内获取必需微量营养素以及该病原体如何在营养饥饿的口腔生物膜内成功竞争的理解。当口腔细菌产生的酸侵蚀牙釉质时，就会形成龋齿。这个过程是由致龋细菌的发酵代谢驱动的，最显著的是 营养物质的获取在竞争激烈的口腔中至关重要，许多生物体已经进化出各种策略来获取碳源或必要的生物分子。核黄素等 B 族维生素是许多口腔链球菌必须从口腔环境中获取的物质，对于在竞争激烈的口腔中生存是必需的。然而，这个过程的主要机制和涉及的蛋白质仍未被描述。这项研究很重要，因为它确定了 核黄素获取和辅因子生成的关键步骤，这可能通过选择性靶向代谢物转运蛋白为开发新型抗龋治疗策略提供依据。
